Experimental and clinical observations have supported the concept that the hypothalamus plays a key role in the regulation of adenohypophysial corticotropic cells secretory functions. Over 25 years ago, Guillemin, Rosenberg and Saffran and Schally independently demonstrated the presence of factors in hypothalamus which would increase the rate of ACTH secretion by the pituitary gland incubated in vitro or maintained in an organ culture. None of the secretagogs characterized met the criteria expected of a physiologic corticotropin releasing factor (CRF) until ovine CRF (oCRF) was characterized in 1981. The formula of 41-residue peptide is disclosed in U.S. Pat. No. 4,415,558.
Sauvagine is a 40-residue, amidated generally similar peptide which was isolated from the skin of the South American frog Phyllomedusa sauvagei. It was characterized by Erspamer et al. and was described in Regulatory Peptides, Vol. 2 (1981), pp. 1-13, wherein its formula is disclosed. Sauvagine and oCRF have been reported to have biological activity in lowering blood pressure in mammals and in stimulating the secretion of ACTH and .beta.-endorphin.
Rat CRF(rCRF) has been isolated, purified and characterized as a hentetracontapeptide; its formula is disclosed in U.S. Pat. No. 4,489,163. It may alternatively be referred to as rat Amunine. The formula of human CRF has now been determined to be the same as that of rCRF. Synthetic rCRF and oCRF stimulate ACTH and .beta.-endorphin activities in vitro and in vivo and substantially lower blood pressure for an extended time period.